Laboratoire de Pharmacologie Médicale et Clinique, Centre Midi-Pyrénées de PharmacoVigilance, de Pharmacoépidémiologie et d'Informations sur le Médicament, Pharmacopôle Midi-Pyrénées, INSERM UMR 1027, CIC INSERM 1436, CHU et Faculté de Médecine de Toulouse, Toulouse, France.
Psychopharmacology (Berl). 2017 Oct;234(20):3075-3081. doi: 10.1007/s00213-017-4685-7. Epub 2017 Aug 3.
QT interval prolongations were described with citalopram and escitalopram. However, the effects of the other serotonin reuptake inhibitors (SRIs) remained discussed. In order to identify a putative signal with other SRIs, the present study investigates the reports of QT interval prolongation with SRIs in two pharmacovigilance databases (PVDB).
Two kinds of investigations were performed: (1) a comparative study in VigiBase®, the WHO PVDB, where notifications of QT prolongation with six SRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) were selected. Cases with overdose or pregnancy were excluded. The relationship between the "suspected" SRI and occurrence of QT prolongation was assessed by calculating reporting odds ratio (ROR) in a case/non-case design. (2) A descriptive study of QT prolongation reports with citalopram and escitalopram in the French FPVD.
In VigiBase®, 855 notifications were identified (mean age 56.2 years, mainly women 73%). Among them, 172 (20.1%) were associated to escitalopram; 299 (35.0%), to citalopram; 186 (21.8%), to fluoxetine; 94 (11.0%), to sertraline; 66 (7.7%), to paroxetine; and 38 (4.4%) to fluvoxamine. A significant ROR value (higher than 1) was only found for citalopram (3.35 CI95% [2.90-3.87]) or escitalopram (2.50 [2.11-2.95]). In the FPVD, eight reports of QT prolongation were found with citalopram and 27 with escitalopram, mainly in women (77.1%) with a mean age of 73.2 years. In 23 cases (66%), SRIs were associated with other suspected drugs, mainly cardiotropic or psychotropic ones. Hypokalemia was associated in six patients.
This study, performed in real conditions of life, shows a clear signal of QT prolongation with only two SRIs, citalopram and escitalopram, indicating that QT prolongation is not a SRI class effect.
西酞普兰和艾司西酞普兰可引起 QT 间期延长。然而，其他选择性 5-羟色胺再摄取抑制剂（SSRIs）的影响仍存在争议。为了确定其他 SSRIs 可能存在的信号，本研究在两个药物警戒数据库（PVDB）中调查了 SSRIs 引起 QT 间期延长的报告。
进行了两种研究：（1）在世界卫生组织药物警戒数据库（VigiBase®）中进行了一项比较研究，其中选择了六种 SSRIs（西酞普兰、艾司西酞普兰、氟西汀、氟伏沙明、帕罗西汀、舍曲林）引起 QT 延长的报告。排除了过量或妊娠的病例。采用病例/非病例设计计算报告比值比（ROR）评估“疑似”SSRIs 与 QT 延长发生的关系。（2）在法国药物警戒数据库（FPVD）中对西酞普兰和艾司西酞普兰引起的 QT 延长报告进行描述性研究。
在 VigiBase®中，共确定了 855 份报告（平均年龄 56.2 岁，主要为女性 73%）。其中，172 份（20.1%）与艾司西酞普兰相关；299 份（35.0%）与西酞普兰相关；186 份（21.8%）与氟西汀相关；94 份（11.0%）与舍曲林相关；66 份（7.7%）与帕罗西汀相关；38 份（4.4%）与氟伏沙明相关。仅发现西酞普兰（3.35 CI95% [2.90-3.87]）或艾司西酞普兰（2.50 [2.11-2.95]）的 ROR 值显著升高（高于 1）。在 FPVD 中，发现 8 例西酞普兰和 27 例艾司西酞普兰引起的 QT 延长报告，主要发生在女性（77.1%），平均年龄为 73.2 岁。在 23 例（66%）中，SSRIs 与其他可疑药物相关，主要是心脏毒性或精神类药物。6 例患者伴有低钾血症。
本研究在实际生活条件下进行，显示只有两种 SSRIs（西酞普兰和艾司西酞普兰）可明确引起 QT 间期延长，表明 QT 延长不是 SSRIs 类药物的作用。
